Since the discovery of cephalosporins and the expanded antibiotic activity associated therewith a considerable research effort has been directed to methods of synthesis of these bicyclic .beta.-lactam containing compounds. Many researchers have sought to prepare cephalosporins from readily available penicillins. A significant break through in this line of research was preparation of desacetoxycephalosporins directly from penicillins by an acid catalyzed thermal rearrangement of penicillin sulfoxides. This process was first described in U.S. Pat. No. 3,275,626 issued Sept. 27, 1966. Since that time there has issued a multiplicity of patents describing improved methods for the conversion of penicillin sulfoxides to desacetoxycephalosporins (derivatives of 7-ADCA). More recent discoveries of S. Kukolja et al. [Journal of the American Chemical Society, 98, 5040 (1976)] and Dr. G. A. Koppel [U.S. Pat. No. 4,029,651 issued June 14, 1977] has made derivatives of 7-ACA available from penicillin starting materials. 3-Halo-3-methylcephams are known compounds and have been used to prepare desacetoxycephalosporin derivatives. 3-Halo-3-methylcephams like desacetoxycephalosporins have been prepared directly from penicillin sulfoxides. Penicillin sulfoxides react, for example, with thionyl chloride at elevated temperatures [See S. Kukolja et al. Journal of the American Chemical Society, 94, 7169 (1972) and 97, 3192 (1975)] to provide 3-chloro-3-methylcepham compounds. Such compounds have also been prepared by chlorination of the corresponding 3-hydroxy-3-methylcephams.
The present invention is directed to a new process for preparation of 3-halo-3-methylcepham compounds. More specifically the present invention embodies a process for preparing 3-halo-3-methylcapham compounds from penicillin derived monocyclic azetidinone mercuric sulfides via their reaction with positive halogenating agents.